Cholangiocarcinoma (CCA) is a notoriously lethal malignancy arising from the biliary tract epithelium. While relatively rare, incidence rates have increased markedly worldwide in the past decade. Although definite risk factors such as primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis have been well- documented, the cause of CCA remains unknown for most cases. An importance of not only genetic alterations but also epigenetic aberrations, including promoter hypermethylation and histone modifications, has been indicated for the processes of carcinogenesis and pathogenesis of CCA. This review focuses on epigenetic mechanisms involved in CCA genesis, with special emphasis on their applicability as potential biomarkers for diagnosis, prognosis and prediction as well as promising targets for novel therapeutic strategies.